title: Ionizing radiation-induced gene expression changes in TP53 proficient and deficient glioblastoma cell lines.
abstract: The genetic heterogeneity presented by different cell lines derived from glioblastoma (GBM) seems to influence their responses to antitumoral agents. Although GBM tumors present several genomic alterations, it has been assumed that TP53, frequently mutated in GBM, may to some extent be responsible for differences in cellular responses to antitumor agents, but this is not clear yet. To directly determine the impact of TP53 on GBM response to ionizing radiation, we compared the transcription profiles of four GBM cell lines (two with wild-type (WT) TP53 and two with mutant (MT) TP53) after 8Gy of gamma-rays. Transcript profiles of cells analyzed 30 min and 6h after irradiation showed that WT TP53 cells presented a higher number of modulated genes than MT TP53 cells. Our findings also indicate that there are several pathways (apoptosis, DNA repair/stress response, cytoskeleton organization and macromolecule metabolic process) in radiation responses of GBM cell lines that were modulated only in WT TP53 cells (30 min and 6h). Interestingly, the majority of differentially expressed genes did not present the TP53 binding site, suggesting secondary effects of TP53 on transcription. We conclude that radiation-induced changes in transcription profiles of irradiated GBM cell lines mainly depend on the functional status of TP53.
authors.affiliation: Department of Genetics, Faculty of Medicine of Ribeirão Preto-FMRP-USP, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: P R D V
authors.initials: PR
authors.lastname: Godoy
authors.forename: S S
authors.initials: SS
authors.lastname: Mello
authors.forename: D A R
authors.initials: DA
authors.lastname: Magalhães
authors.forename: F S
authors.initials: FS
authors.lastname: Donaires
authors.forename: P
authors.initials: P
authors.lastname: Nicolucci
authors.forename: E A
authors.initials: EA
authors.lastname: Donadi
authors.forename: G A
authors.initials: GA
authors.lastname: Passos
authors.forename: E T
authors.initials: ET
authors.lastname: Sakamoto-Hojo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012518:Sarcomeres / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: ChIP; DNA damage responses; DNA microarrays; DNA repair; DSBs; FDR; GBM; Glioblastoma; HRR; Ionizing radiation; MT; NHEJ; PET; REST; SAM; SSBs; TP53 gene; WT; chromatin immunoprecipitation; double-strand breaks; false discovery rate; glioblastoma; homologous recombination repair; mutated; non-homologous end joining; paired-end tags; qPCR; quantitative real-time PCR; relative expression software tool; significance analysis of microarray; single-strand breaks; wild type